Ron Keren, MD, FRCPC, Third CCD Chair Clinical Director, University Health Network and Whitby Mental Health Centre Memory Clinics; Assistant Professor, University of Toronto, Toronto, ON.

The Third Canadian Colloquium on Dementia (CCD) was held at the Ottawa Westin, October 27-29, 2005. Over 500 registrants gathered from across Canada and from around the world to participate in this two-and-a-half day event that featured presentations from key international and national experts on dementia. An audience comprised primarily of specialists involved in the diagnosis and management of individuals with dementing disorders was exposed to a broad range of topics delivered in plenary sessions, debates, workshops, and clinicopathological vignettes. The CCD has grown from 150 to 500 registrants over the span of four years, confirming the importance of a national conference on dementia geared primarily towards physicians in this field.
The composition of the third CCD’s organizing committee reflected a broad representation of specialists and their national organizations, including the Canadian Academy of Geriatric Psychiatry (CAGP), the Canadian Geriatrics Society (CGS), the Canadian Neurological Society (CNS), and the Consortium of Canadian Centres for Clinical Cognitive Research (C5R), as well as representatives from neuropsychology and family medicine. The program of the third CCD was tailored to the guidelines of the Royal College of Physicians and Surgeons for accredited group learning. The content of the program was driven by a needs assessment completed at the second CCD.

Program Highlights
The third CCD was opened with a colourful presentation by Dr. Jock Murray from Dalhousie University titled “When the National Leader Becomes Forgetful.” Dr. Murray was the only non-American invited to participate in the Working Group on Disability in US Presidents formed by President Clinton. Dr. Murray gave a historical account of international leaders whose medical conditions affected their abilities to lead. Dr. Murray explained that, historically, when leaders became seriously ill they were dealt with by the “Captive King Syndrome”; they remained in office and their illness was kept hidden while those around the leader took charge. Under these circumstances the judgements of their physicians were political rather than medical. Dr. Murray pointed out that physicians have often been part of the problem by feeling a duty towards the leader as opposed to society. “They believe that their leader sick is better than the competition well.”

Dr. Murray’s presentation was followed by Dr. Peter St. George-Hyslop from the University of Toronto. Dr. St. George-Hyslop, a regular speaker at the CCD, gave an update on research pertaining to Ab-directed therapies for Alzheimer’s disease (AD) based on evidence from the amyloid cascade theory of AD. Dr. St. George-Hyslop explained that A‚ is formed through the misprocessing of the amyloid precursor protein. This pathological pathway involves both beta and gamma secretases. Subsequently, attempts are being made to inhibit these two enzymes in the hopes of diminishing the accumulation of Ab. While appearing to be very hopeful strategies, Dr. St-George Hyslop pointed out that a number of serious obstacles related to the development of these therapies have been observed in transgenic mice. He also discussed the potential clearance of Ab through the Ab vaccines and reviewed the follow-up studies on the phase 2a vaccine trial that was abruptly discontinued due to the occurrence of encephalitis in a number of the subjects receiving the vaccine. Unfortunately, results of the cognitive outcome measures in patients who developed an immune response in the study were not statistically significant. However, as Dr. St. George-Hyslop pointed out, due to the early discontinuation of the study the subjects did not receive the full complement of A‚ injections. Despite these discouraging results, Dr. St. George-Hyslop believes that the A‚ vaccine still holds promise as a therapeutic agent for AD, through active immunization with a modified A‚ protein or passive immunization with monoclonal antibodies. Lastly, Dr. St. George-Hyslop discussed another A‚-directed therapy that would inhibit the development of neurotoxic A‚ protofibrils. While addressing the importance of A‚ in the development of AD, Dr. St.-George Hyslop pointed out that the clinical symptoms of AD are more highly correlated with tau pathology than with beta amyloid: “You can be chock full of amyloid and not have dementia.” Nevertheless, A‚ is still considered to be the likely cause of a cascade of events leading to the development of the tangles and neuronal death that are present in AD.

Presentations by Dr. Serge Gauthier (McGill University) and Dr. Kenneth Rockwood (Dalhousie University) as well as a workshop lead by Dr. Gary Naglie (University of Toronto) highlighted current therapies for AD and how their benefits are measured in clinical drug trials. Both Drs. Rockwood and Naglie discussed the recent literature critiquing the cholinesterase inhibitors (ChEIs), pointing out that despite numerous successful RCTs these treatments have not been fully embraced. While the buzz in the audience suggested that this might be explained in part by ageism, both Drs. Rockwood and Naglie believe that the choice of outcome measures may be a factor. Dr. Rockwood reviewed some of his recent research on the Goal Attainment Scale (GAS) and Dr. Naglie reviewed the importance of Quality of Life scales as well as milestone scales, such as the time to placement in long-term care.

Dr. Donald Stuss (University of Toronto) and Dr. Ron Peterson (Mayo Clinic College of Medicine) gave presentations on the predementia stages, normal aging, and mild cognitive impairment. Dr. Stuss discussed factors that affect our memory, such as the time of day. He discussed “morningness-eveningness” distributions, reporting on evidence that shows that college students are mostly evening types with very few morning types whereas older adults are morning types with very few evening types. Dr. Stuss also reported that difficulties with retrieval appear to be a common manifestation of aging. In closing, Dr. Stuss pointed out that wisdom does not deteriorate with aging and that cognitive rehabilitation can be used to overcome some of the observed deficits associated with aging.

Two presentations on depression were delivered by Dr. Ira Katz (University of Pennsylvania) and Dr. Lilian Thorpe (University of Saskatchewan). Dr. Katz reviewed his work on depression in long-term care (LTC). He showed that the ratings of depression with residents and staff were totally uncorrelated. Dr. Katz concluded that screening and recognition for depression should be based on hearing the resident’s voice whenever possible. In discussing the treatment of depression in LTC, Dr. Katz pointed out that over the years there has been a dramatic increase in the use of antidepressants (from 12.6-24.9% of cases); however, there has been no improvement in getting treatment to work. He concluded by suggesting that minor depression in LTC should be treated with watchful waiting and by activating the facility resources such as care strategies, routines, preferences, activities, and family involvement. Dr. Thorpe’s presentation focused on depression in dementia. She discussed the heterogenic and overlapping etiologies of depression in dementia as well as the diagnostic challenges in differentiating between the overlapping symptoms of depression and dementia. For example, Dr. Thorpe mentioned that the core depressive symptoms of guilt and worthlessness are significantly less common in dementia. In closing, Dr. Thorpe gave an excellent review of the evidence for the pharmacological treatment of depression in dementia.

Dr. Mary Mittelman, New York University School of Medicine, presented her research on caregiver interventions in dementia through the NYU Caregiver Intervention Study. Dr. Mittelman’s research has shown that psychosocial interventions can lead to a decline in caregiver symptoms of depression, an improvement in the caregiver’s reaction to problem behaviours, and a delay of almost one year to LTC placement.

Drs. Anthony Lang (University of Toronto) and Clive Ballard (University of Newcastle upon Tyne) reviewed the latest literature on Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Both speakers emphasized that these two conditions have been arbitrarily differentiated from each other based on the “one-year clause,” while in all likelihood they are different clinical manifestations of the same disease. Dr. Lang described a new face to Parkinson’s disease. PD is not a single disease as has been previously conceived. The new face of PD recognizes that the pathology of PD extends beyond the substantia nigra. Once the motor features of the disease are eliminated, the patient is left with clinical features such as apathy, dementia, and postural instability. Dr. Lang concluded that major advances and improvement in current responses to symptomatic therapies are less likely to come from a focus on dopamine deficiency in the substantia nigra than they are from attention to the nondopaminergic features. Dr. Ballard gave an excellent update on DLB, discussing the difficulties in making a clinical diagnosis with the current diagnostic criteria having high specificity but low sensitivity. The high prevalence of tau pathology in DLB substantially contributes to the variability in its clinical presentation. As Dr. Ballard put it, “the more tau present, the less likely the patient will be diagnosed with DLB.” Dr. Ballard also discussed antiproteosomal treatments as a future direction for the treatment of DLB.

Dr. Morris Freedman (University of Toronto) provided the audience with a video-packed presentation on frontotemporal dementia and Dr. Sandra Black (University of Toronto) reviewed the state of the art pertaining to neuroimaging in Alzheimer’s disease. Michelle Tremblay (University of Ottawa) helped the audience conceptualize issues around capacity, emphasizing the importance of the two key components: “understanding and appreciating.” Dr. Malcolm Man-Son-Hing, also from the University of Ottawa, reviewed the sensitive issue of driving and dementia. According to Dr. Man-Son-Hing, decision making about driving involves balancing safety and quality of life.

Dr. Gustavo Roman (University of Texas) delivered a presentation on “The Shifting Limits between Vascular Dementia (CVD) and Alzheimer’s Disease.” Dr. Roman described the importance of CVD in the expression of dementia in patients with AD pathology. He stressed the importance of treating vascular risk factors in the possible prevention of dementia onset and its progression.

The audience of the third CCD was treated to very stimulating debates on two hot clinical topics. Drs. Nathan Herrmann (University of Toronto) and Dr. Ira Katz debated in favour of the resolution “Treatment of Behaviour in Dementia with Atypical Neuroleptics: Benefits Outweigh Risks” while Drs. Jiska Cohen-Mansfield (George Washington University) and Clive Ballard debated against the resolution. Despite excellent arguments on the efficacy and relative safety of these agents from Drs. Herrmann and Katz, it was Drs. Cohen-Mansfield and Ballard who seemed to change most of the opinions in the audience through their claims that behavioural interventions have not been sufficiently utilized and the concerns they raised about the safety of atypical neuroleptics in older adults. However, both sides agreed that there are cases where safety is of a major concern, and a role for atypical neuroleptics cannot be disputed.

Dr. Howard Chertkow (McGill University), who was in favour, and Dr. Ron Petersen (Mayo Clinic College of Medicine), who was opposed, debated the resolution: “Cholinesterase Inhibitors Should Be Used to Treat Mild Cognitive Impairment.” Through a number of case presentations, Dr. Chertkow managed to change many of the opinions in the audience, suggesting that evidence-based medicine and clinical medicine are not always one and the same.

The third CCD wrapped up with an opportunity for the audience to demonstrate the knowledge they gained from the conference through clinicopathological vignettes presented by Drs. Howard Feldman and Ian MacKenzie from the University of British Columbia.

While still savouring the success of the third CCD, the organizing committee is already working hard on the program for the fourth CCD, to be held in Vancouver, British Columbia from October 18-20, 2007. We look forward to seeing you there!

The Third CCD gratefully acknowledges unrestricted educational grants from Janssen-Otho Inc., Lundbeck Canada, Novartis Canada, and Pfizer Canada.

No competing financial interests declared.

First Pharmacy Conference at Baycrest Centre for Geriatric Care

Christine Oyugi, BSc, Managing Editor, Geriatrics & Aging.

Speakers

1. Osteoporosis Update:
   Tom Brown, PharmD, Pharmacist, Women's Health Pharmacy Department, Sunnybrook & Women's College Health Sciences Centre, Toronto, ON.
2. Diabetes and the Elderly:
   Dr. Christine Papoushek, PharmD, University Health Network, Department of Family and Community Medicine/Pharmacy, Toronto, ON.
3. Pharmacological Management of Congestive Heart Failure:
   Fran L. Paradiso-Hardy, BScPhm, MSc Pharm, Clinical Co-ordinator/Infectious Diseases, Department of Pharmacy, Sunnybrook Health Sciences Centre, Toronto, ON.
4. New Evidence and Guidelines in Osteoarthritis:
   Natalie Kennie, PharmD, Primary Care Pharmacist, St. Michael's Hospital Health Centre, Toronto, ON.

Elderly patients are at high risk for medication-related problems due to age-related physiological changes, a higher incidence of comorbid illnesses and greater use of both prescription and over-the-counter medications. As a result, older adults are at increased risk of developing adverse drug events. It is important for physicians to regularly review the drug regimen of any older patient, in order to determine if the drug is effective, monitor for adverse drug events and recommend newer alternative therapies, as they become available. These points were addressed at the 'First Pharmacy Conference on Medication Use in the Geriatric Population' held at the Baycrest Centre for Geriatric Care. This article summarizes some of the major points addressed at this conference.

I. Osteoporosis Update

The objectives of this talk were to illustrate the role of combination therapy in the management of osteoporosis; discuss the value of guidelines in managing osteoporosis; and demonstrate the application of new evidence to managing complex patients. Dr. Brown presented four case studies by way of achieving these objectives.

Case Synopses
Case One
A 57-year-old Caucasian female who has been on Hormone Replacement Therapy (HRT) for the past four years for vasomotor symptoms. She was diagnosed with osteopenia two years ago and takes conjugated equine estrogen (CEE) 0.625mg, and Medroxyprogesterone acetate 2.5mg daily. She has a familial history of osteoporosis, myocardial infarct (MI) and breast cancer, and smokes a pack of cigarettes a day. Her BMD was -2.3 spine and -1.8 hip in January 2000, -2.6 spine and -2.2 hip in January 2002.

Should we add a bisphosphonate to the HRT regimen? Several studies indicate beneficial effects of adding a bisphosphonate to ongoing HRT in postmenopausal women. Patients on HRT and etidronate have a significantly greater BMD when compared to women on monotherapy. A study of 428 postmenopausal women with osteoporosis, who had been receiving HRT for at least one year, demonstrated that adding a bisphosphonate (alendronate) significantly increased bone mass at both spine and hip trochanter.¹ Therefore, patients who have failed both HRT and bisphosphonate monotherapy should be considered for combination therapy. Although BMD improves, several sub-group analyses demonstrate that changes in BMD cannot fully account for anti-fracture efficacy.

Case Two
A 70-year-old Asian women with osteoporosis. Her mother fractured a hip at the age of 86 years and her father developed colon cancer at 64 years. Her BMD is spine -2.8 and hip -1.9. Her total cholesterol is 6.85 mmol/L, LDL 4.97mmol/L, HDL 1.32 mmol/L and triglyceride 1.84mmol/L.

Currently, several guidelines exist for the treatment of osteoporosis. Unfortunately, the guidelines have varying recommendations, are often outdated and tend to focus on risk factors and initiating therapy, without proper advice on monitoring or follow-up. The guidelines from several organizations are listed below:

1. The National Osteoporosis Foundation (NOF)--First consider HRT and then Alendronate in patients who are unwilling or unable to take HRT, or who fail on HRT. If both bisphosphonates and HRT fail, then consider calcitonin. Raloxifene, a selective estrogen-receptor modulator (SERM), is given as an alternative therapy.
2. The American Association of Clinical Endocrinologists (AACE)--First priority is given to FDA-approved medications for prevention and treatment. There is level 1 evidence that bisphosphonates, calcitonin and raloxifene decrease vertebral hip fractures.
3. The Ontario Program for Optimal Therapeutics (OPOT)--Try estrogen, bisphosphonate or SERM. If unable to take any of the three, or if immobilized and with acute fracture, try calcitonin.
4. The Osteoporosis Society of Canada's guidelines, which are in the process of being developed, suggests the use of bisphosphonates and raloxifene. For this case, Dr. Brown suggests the use of raloxifene.

Case Three
A 65-year-old Caucasian male with osteoporosis indicated by a BMD of -2.4 spine and -2.6 hip. His medications are actenolol, enalapril, atorvastatin and ASA. He had an MI at 45 and stopped smoking 10 years ago.

For Case three, the NOF and the AACE have no recommendations. The OPOT would suggest starting the patient on a bisphosphonate; a decision supported Dr. Brown. If the patient is hypogonadal, add testosterone and consider calcitonin if he is immobilized with acute pain. Studies indicate beneficial effects of using a bisphosphonate in men with osteoporosis.

Case Four
An 83-year-old Caucasian woman who resides in a nursing home. Her health is poor and although she walks, she has difficulty getting out of a chair. There is no information on her BMD but she has had one fall in the past year.

According to the NOF guidelines, for women who are at least 70 years of age and have multiple risk factors, treatment can be initiated without BMD. Studies show that bisphosphonates, calcium and Vitamin D are beneficial for preventing hip fractures. A study on the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures (n=3270) found that hip fractures were 43% lower, and non-vertebral fractures were 32% lower, in the treatment group when compared to placebo.2 So, in this case it may be beneficial to start calcium and vitamin D therapy and perhaps the use of hip protectors.

Case Five
A 56-year-old woman started HRT four years ago for prevention of heart failure (HF) and cardiovascular disease (CVD). She had an MI 18 months ago and discontinued the HRT for three months. She then started again due to vaginal dryness. She was diagnosed with osteoporosis two years ago (BMD: spine -3.0, hip:-2.5 and had not changed in two years). Total cholesterol 52mmol/L, LDL: 2.8mmol/L, HDL: 1mmol/L and TG 2.8 mmol/L)

Should the patient stay on estrogen or should another agent be added? There is no evidence with estrogen that maintaining BMD is sufficient to reduce hip fracture. She has been on HRT for four years (with the exception of the three-month break) and her BMD has remained constant for two years. The Heart and Estrogen/progestin Replacement Study (HERS) trial examined whether estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease.³ No significant difference was found between groups on non-fatal and fatal CHD, leading the authors to recommended against starting this treatment for the purpose of secondary prevention of CHD. However, over four years, there was a trend toward fewer CHD events in the treatment group; thus, it could be appropriate for women already receiving this treatment to continue. Another study looked at the effect on quality of life of estrogen plus progestin therapy used as secondary prevention in women with coronary artery disease.⁴ The effects of hormone therapy depended on the presence of menopausal symptoms; women without flushing had greater declines in physical measures, while women with flushing had improvements in emotional measures of quality of life. For Case five, it is recommended to stop the HRT and initiate bisphosphonate therapy. Use Raplens® or Estring® for the vaginal dryness.

II. Diabetes and the Elderly--How low can you really go?

Treatment of elderly patients with Diabetes Mellitus (DM) is complicated. The aim of this talk was to address two important considerations when treating the elderly patient:

1. How low can we go (referring to blood glucose levels)?
2. Which medications are optimal for treating the elderly and why?

The prevalence of diabetes increases with age, approaching 20% in Caucasian patients over the age of 70, and in certain ethnic groups, is as high as 50%.⁵ Many members of the general population have undiagnosed diabetes or have impaired glucose tolerance. Most elderly patients with diabetes are asymptomatic and are diagnosed during a routine visit to the physician's office or after being hospitalized for a complication of diabetes. Most of these patients have Type 2 diabetes and can present with any of the three conditions that are present in most diabetic patients--hypertension, coronary heart disease and hyperlipidemia. However, for the elderly patient, multiple comorbid illnesses, as well as the issue of polypharmacy, may impact the type and extent of treatment.

DM is the sixth most common cause of death among the elderly. Patients with DM have an increased risk of macrovascular and microvascular disease when compared to non-diabetic elderly persons. Longitudinal studies have demonstrated that mortality is strongly correlated with variability in blood glucose and HbA1c, similar to what is seen in the younger diabetic population. DM is a strong indicator of functional decline and has also been correlated with decreased quality of life, increased chronic disease and an increase in utilization of health care resources when compared to non-diabetic elderly. The primary reasons for treating diabetes are improvement of symptoms and avoidance of associated complications (Table 1).

Several studies show that tight control of blood glucose is important for decreasing the long-term complications of DM, and the risk of hypoglycemia in the elderly, which can have serious short-term effects.^6-8 The Diabetes Control and Complications Trial (DCCT)⁶ was conducted to determine whether intensive therapy (with an aim to maintain normal glucose and HbA1c concentrations) could prevent or delay long-term complications in patients with Type 1 DM. The trial showed that during an average treatment period of 6.5 years, the risk of the development or progression of early microvascular complications of diabetes was substantially lower in the intensive-therapy group relative to the conventional-therapy group. Another randomized controlled trial, the United Kingdom Prospective Diabetes Study (UKPDS),⁷ compared the effects of intensive blood-glucose control with either sulfonylurea or insulin to conventional treatment on the risk of microvascular and macrovascular complications in patients with Type 2 diabetes. Intensive blood-glucose control by either sulfonylureas or insulin substantially decreased the risk of microvascular complications, but not macrovascular disease, in this group of patients. There are some limitations to these trials. The UKPDS used newly-diagnosed patients that were treatment naïve and had less severe disease. Patients with significant comorbid illnesses were excluded, as were elderly patients (over 65 years of age). The DCCT looked at patients with Type 1 DM with a mean age of 27 years.⁶

There are some specific issues that must be taken into consideration when treating a patient with DM. First, the individual treatment goals must be defined early on. The Canadian Diabetes Association's guidelines for glucose control give a target of 4-7% mmol/L preprandial glucose. Are you trying to achieve symptom control or prevent complications? The extent and impact of comorbidities such as CAD, microvascular complications, functional limitations and disabilities, as well as cerebrovascular and peripheral vascular disease must also be considered. The aforementioned can all affect the ability to achieve tight blood glucose control, an individual's ability to take medication and adherence to a specific regimen. It is also important to assess the risk of and treat hypoglycemia. When reviewing the treatment options, one must also consider the patient's life expectancy and the time frame in which the benefits of treatment will be achieved.

So what are the treatment options for the elderly? A number of drug therapies are available (Table 2). Sulfonylureas or Metformin are the first drugs of choice followed by Glitazones, Glitinide, Acarbose and Insulin.

To summarize, the goal of treating diabetes in the elderly can be similar to that of younger people, to go "low." However, multiple factors and comorbid conditions need to be considered on an individual basis. The goal of treatment should be to maximize benefits and minimize risk.

III. Pharmacological Management of Congestive Heart Failure: Drug Interactions, Comorbid Conditions and New Therapeutic Options

There are numerous drugs that may potentially induce Congestive Heart failure (CHF) in patients with normal ventricular function and/or precipitate heart failure in patients with compensated CHF. Many heart disease patients are elderly and have concomitant diseases requiring multiple medications. It is estimated that medications with contraindications or precautions for use are administered to up to 15% of patients with heart failure. Table 3 gives a summary of the drugs associated with precipitating HF. This talk concentrated on the risk of CHF associated with the use of Non-steroidal anti-inflammatory drugs (NSAIDs)--including COX-2 inhibitors.

NSAIDs are the most widely used therapeutic agents in the elderly, generally for the management of osteoarthritis and rheumatoid arthritis. NSAIDs reversibly inhibit the cyclooxygenase (COX) enzyme and prevent the biosynthesis of prostaglandins. In patients with HF, prostaglandin synthesis is an important compensatory mechanism for the maintenance of cardiovascular and renal homeostasis. By blocking the synthesis of prostaglandins, NSAIDs may interfere with renal homeostasis inducing or exacerbating HF. NSAIDs also interact with Angiotensin Converting Enzyme (ACE) inhibitors. Both angiotensin II (efferent arteriole vasoconstrictor) and prostaglandins (afferent arteriole vasodilator) play a role in preserving renal function. ASA has been reported to reduce efficacy of ACE inhibitors, so it is advisable to limit ASA dose to less than 100 mg per day in HF patients receiving an ACE inhibitor. There is also an increased risk of hyperkalemia with concomitant use of NSAIDs and ACE inhibitors.

The COX-1 enzyme is present in most tissues, and functions as a housekeeping enzyme, increasing prostaglandins that mediate homeostatic functions such as platelet activation, renal perfusion and maintainence of normal gastric mucosa. Blocking COX-1 can result in serious gastrointestinal adverse effects. COX-2 is induced by inflammation and increases prostaglandins that mediate pathologic effects such as local inflammation, pain and fever. COX-2 also increases prostaglandins that mediate renal homeostasis. The development of newer COX-2 selective drugs has allowed for relief of pain and inflammation without the adverse effects associated with COX-1 blockade. However, by decreasing vasodilatory and antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased prothrombotic activity. A meta-analysis of trials (including the Vioxx Gastrointestinal Outcomes Research Study (VIGOR; 8076 patients)) and the Celecoxib Long-term Arthritis Safety Study (CLASS; 8059 patients) found that the annualized myocardial infarction rates for patients taking COX-2 inhibitors in both VIGOR and CLASS were significantly higher than those in the placebo group.⁹ The available data raise a cautionary flag regarding the risk of cardiovascular events with COX-2 inhibitors and further prospective trial evaluation may characterize and determine the magnitude of the risk.⁹

There are a number of risk factors for NSAID renal toxicity. These include pre-existing renal disease, renal hyperfusion and concomitant drug therapy (diuretics and antihypertensives). NSAIDs have been associated with hospitalization for congestive heart failure.^10,11 In patients with pre-existing HF, use of NSAIDs is associated with a substantially increased risk of a relapse. It has also been reported that the risks are greatest for NSAIDs with a long half-life (naproxen, piroxicam).

Uncontrolled hypertension is a precipitating factor for HF in 44% of patients.¹¹ NSAIDs cause sodium and water retention (fluid retention 05-1L; weight gain 1-2 kg). NSAIDs also inhibit synthesis of prostacylin (PGI2) and increase peripheral resistance. Thus, they can elevate blood pressure, especially in those patients who have pre-existing hypertension. Studies also report that NSAIDs blunt the therapeutic effects of antihypertensive medications.¹¹

Approximately 10% of elderly patients use NSAIDs and diuretics at least once a year. NSAIDs can alter the therapeutic effects of diuretics, especially in patients with depleted sodium levels. There is also an increase risk of hyperkalemia with concomitant use of NSAIDs and spironolactone.

Therefore, NSAIDs (including COX-2 inhibitors) must be used with caution in patients with HF and wherever possible, alternative pharmacologic agents should be used. If an NSAID is indicated, the patient should be informed of the potential risks and need for regular monitoring of serum creatinine, body weight and signs and symptoms of HF. There are a number of new therapeutic options. Table 4 summarizes the new options available.

IV. New Evidence and Guidelines in Osteoarthritis (OA)

Using a "typical" case, Dr. Kennie identified management issues for the use of pharmacologic alternatives in OA in the elderly. She outlined the recent changes in guidelines for the management of OA and the supporting evidence, and discussed common management issues for specific pharmacalogic alternatives in the elderly.

Case: OTIS
A 67-year-old retired stockbroker who has had osteoarthritis in his knee for the last three years. Recently, his knee pain has worsened and he has noticed stiffness and soreness for 30 minutes when he wakes up in the morning or after sitting for long periods. He has some pain at rest and has noticed a clicking sound when he walks. Otis probably has mild OA. He has been taking acetaminophen 500 mg, 1-2 tablets three times a day on most days and feels that it is somewhat useful.

Osteoarthritis (OA) is a slowly progressive disorder of the joints; very little inflammation is involved in the early stages, although some believe that there is inflammation at the molecular level. OA most commonly involves the hands, feet, spine and weight-bearing joints such as the knees and hips. There are two main factors that lead to joint failure. The first is progressive breakdown of articular cartilage that lines joint surfaces, which is associated with pain and disability. The second is the formation of dense, smooth surface bone at the base of the cartilage lesion and the formation of osteophytes. The goals of therapy for OA should be to control pain, maintain joint function, reduce disability and improve health-related quality of life. The question is when to treat and with what? This depends on the severity of the OA pain. Guidelines on pharmacologic therapy suggest the following:

1. The use of Acetaminophen for mild-to-moderate OA (where pain occurs occasionally). Acetaminophen has an analgesic role, but is not an anti-inflammatory agent. Acetaminophen has demonstrated similar efficacy to NSAIDs for relief of mild-to-moderate OA,¹² and is a safer, lower cost alternative. Acetaminophen has the added benefit of being used on either an as needed or regular basis. However, it should be used with caution in patients consuming excessive alcohol or in patients with liver damage. For adequate OA control, a dose of 1g qid is required.
2. For moderate-to-severe OA pain (pain occurring more frequently, with some disability), NSAIDs should be considered when symptoms are not adequately controlled by acetaminophen. This higher efficacy of NSAIDs may relate to the fact that inflammation is occurring in OA earlier than was previously believed. Patients tend to prefer NSAIDs, which are superior to acetaminophen for pain at rest and pain on motion.² There are several types of NSAIDs (salicylates, traditional, and COX-2 selective NSAIDs) and they are generally equivalent in efficacy for OA pain at comparable doses. The agents with a longer half-life may provide better pain control (e.g. meloxicam).
3. For single joint involvement, topical analgesics and intra-articular injections can be considered.

Certain factors must be taken into consideration when prescribing NSAIDs for elderly patients, including the risk of GI toxicity, the risk of renal toxicity, congestive heart failure or high blood pressure. Inhibition of COX-1 can lead to gastrointestinal mucosal injury. In patients over 65 years, research shows that 20-30% of all hospitalizations and deaths due to peptic ulcer disease were attributable to NSAIDs.¹⁴ It has also been reported that 20-25% of patients experience dyspepsia during therapy, the severity of which is unrelated to the severity of the mucosal injury. The risk factors for GI toxicity include: previous peptic ulcer disease, age over 65 years, concomitant use of warfarin or corticosteroids, comorbid illness, chronic alcoholism and the use of multiple medications. For high-risk patients, it is recommended to use COX-2 selective inhibitors or a traditional NSAID plus a gastroprotective agent (e.g. PPI).

Other agents may also be used for OA. Narcotic analegesics^13,15 relieve pain but lack anti-inflammatory properties. They are generally used to provide short-term analgesia when pain has become very severe. They may also be considered in patients who do not respond or have contraindications to acetaminophen or NSAIDs, or are not candidates for surgery for chronic pain management. Patients may experience adverse effects such as nausea, constipation, dizziness or drowsiness.

Recently, there has been new evidence on the use of glucosamine sulfate.^16,17,18 Glucosamine is believed to stimulate the production of cartilage and prevent its destruction by inflammatory mediators and enzymes. Glucosamine can be beneficial in reducing pain (mild-to-moderate) in OA patients. One study suggested that it may slow the progression of OA in the knee;¹⁸ however, the agent used in the study was an oral form of a specific glucosamine crystalline product made in Belgium. The usual dose is 1500mg/day (od or tid) and the full effects are not seen for 4-6 weeks. A common side effect is GI upset. Glucosamine should be used with caution in patients with diabetes due to potential inteference with glucose control.

References

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4. Hlatky MA, Boothroyd D, Vittinghoff E, et al. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA. 2002; 287:591-7.
5. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The third national health and nutrition examination survey, 1988-1994. Diabetes Care 1998;21:518-24.
6. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 2000;342:381-9.
7. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-53.
8. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995 28:103-17.
9. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001;286:954-9.
10. Feenstra J, Heerdink ER, Grobbee DE, et al.Association of Nonsteroidal Anti-inflammatory Drugs With First Occurrence of Heart Failure and With Relapsing Heart Failure.The Rotterdam Study Arch intern Med 2002;162-265-70.
11. Page J, Henry D. Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients : An Underrecognized Public Health Problem. Arch intern Med 2000;160:777-84.
12. Bradley JD, Brandt KD, Katz BP, et al. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med. 1991;325:87-91.
13. Tannenbaum H, Peloso PM, Russell AS, Marlow B. An evidence-based approach to prescribing NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis: The Second Canadian Consensus Conference. Can J Clin Pharmacol. 2000;7 Suppl A:4A-16A. Review.
14. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxiciy of nonsteroidal antiinflammatory drugs. N Engl J Med 1999;340:1888-99.
15. Canadian Pain Society. Use of opioid analgesics for the treatment of chronic noncancer pain. Pain Res Mang 1998;3:197-208.
16. da Camara CC, Dowless GV. Glucosamine sulfate for osteoarthritis. Ann Pharmacother. 1998 May;32:580-7. Review.
17. McAlindon TE, LaValley MP, Gulin JP et al. Glucosamine and chrondroitin for treatment of osteoarthritis: A sytematic quality assesement and meta-analysis. JAMA. 2000;283:1469-75.
18. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357:251-6.

Dr J. Holroyd-Leduc, MD, FRCPC
Dr. M. Reddy, MD, FRCPC
Associate Editor,
Geriatrics & Aging.

Osteoporosis and the Frail Elderly

• According to prevalence data from 1993, based on bone mineral density assessments 1.4 million Canadian women had osteoporosis and over 60,000 women were estimated to have osteoporosis-related fractures that year.
• In those over 65, the projected number of hip fractures in Canadians over 65 will increase from 12% in 1993 to 25% in 2041.
• The mean one-year cost of a hip fracture is $26,527 (CAN) based on an observational study conducted by Wiktorowicz, et al. (Osteo Int;2001:12(4)).
• Bisphosphonates are the only agents documented to reduce hip fracture risk in calcium and vitamin D replete adults with osteoporosis.
• Non-pharmacological strategies shown to be effective include correcting calcium and vitamin D deficiency in the very elderly, use of hip protectors in fall-prone individuals, and fall-prevention programs in nursing homes.

Prevention in Geriatric Care

• Exercise programs reduce falls and fall-related injury by 35% and are most effective in those 80 years and older.
• Some preventative targets in the elderly, other than disease-specific issues, include disability, frailty, inappropriate LTC admission and hospitalization, "nosicomal" delirium and deconditioning, and inappropriate drug use.

Influenza and Superbugs in the Nursing Home

• 80-90% of influenza-related morbidity and mortality occurs in older adults.
• Vaccination is only 50-60% effective for preventing illness in older people, however it is 80-90% effective at preventing serious complications.
• Influenza in the elderly can present atypically, lower respiratory tract involvement is common, and constitutional symptoms can be prolonged resulting in disability.
• Superbugs, which includes MRSA and VRE, can be controlled effectively with appropriate universal hand- washing (patients, staff, visitors, and volunteers) and without requiring isolation.

Osteoarthritis

• Risk factors for developing osteoarthritis include advancing age, female sex, bent knee activities, heavy lifting, muscle weakness, absence of osteoporosis, genetic predisposition, obesity and possibly recreational sports.
• Nonpharmacological management therapies of variable effectiveness include weight loss, exercise, orthoses, education, Glucosamine, vitamin C, vitamin D and transcutaneous electrical nerve stimulation (TENS).
• Pharmacological treatment in the elderly should include consideration of a trial with regular dosing of acetaminophen. The main issues of concern with acetaminophen use includes compliance, variable effectiveness, and potential for liver toxicity.
• Cox-2 inhibitors are another option in the elderly. They appear to demonstrate less gastrointestinal toxicity than do traditional NSAIDS; however they still have the potential for renal toxicity, hypertension and peripheral edema. Coxibs should be used with caution in individuals with a history of gastrointestinal ulcers; concomitant use of NSAIDs, anticoagulants or steroids; age over 60; and/or a history of heart disease.

Non-Alzheimer Dementia: Frontal Temporal

• Diagnosis can be divided into Frontotemporal dementia (socially inappropriate behaviour, perseveration, and stereotypic behaviour); Primary progressive aphasia; Corticobasal degeneration (atypical extrapyramidal-apraxic syndrome); Semantic dementia (loss of meaning of things, loss of comprehension and naming). However, different subtypes can co-occur in the same individual.
• There is evidence of serotonin deficiency in Frontal Temporal dementias.
• The frontal system is responsible for executive control, and executive dysfunction leads to problem behaviour.
• One form of bedside testing includes the CLOX test, where an individual is asked to draw an unprompted clock, copy a clock and draw intersecting pentagons. An individual with executive dysfunction can copy but will have impairment in unprompted clock drawing, compared to an individual with Alzheimer disease who will demonstrate difficulties in both copying and unprompted clock drawing.
• There are few studies that examine clinical management of Frontal Temporal dementia, and the available studies are open-label and case series
  see Table 1.

Diabetes Mellitus

• Incidence is 20% in persons 75 years and older.
• Mortality in elderly diabetics is not dramatically higher compared to age-matched non-diabetics. However there are morbidity benefits from glycemic control. There is an association between elevated Hgb A1C and retinopathy, and elevated Hgb A1C and coronary artery disease.
• Suggested goals of therapy in healthy elderly are FBS <7 and Hgb A1C < 15% above upper limit of normal; the goals in the frail elderly are FBS <10 and Hgb A1C < 40% above the upper limit of normal.
• The DECODE study found that postprandial glucose is an independent risk factor for mortality and cardiovascular disease in type 2 diabetics and in non-diabetics. It also found that most of the excess mortality and cardiovascular risk associated with high fasting glucose depends on simultaneous high 2-hr postprandial glucose.

Congestive Heart Failure

• A model of chronic disease management in the community has been developed in Vancouver, BC, Canada that encompasses an integrated algorithmic approach to the management of heart failure.

The Masks of Depression in the Elderly

• Depression, apathy, delirium, dementia and grief are all separate clinical entities but can co-occur.
• Apathy, depression and delirium can all be manifestations of frontal lobe dysfunction.
• Depression is the most common psychiatric disorder in the elderly, and depression can develop at any point in the lifespan.
• Depression often coexists with medical conditions (stroke 30%; MI 18%; Hip fracture 50%; pain 50%) and it can interfere with the treatment of other medical conditions.
• Depression is not uncommon in patients with Alzheimer dementia and will respond to treatment.
• In early stages of Alzheimer disease the individual complains of a sad mood and feelings of worthlessness, and will appear sad and/or irritable.
• In late stages of Alzheimer disease the individual will appear sad and will have vocalizations of discomfort.

Disturbing Behaviour in Dementia

• in managing aggression and psychosis in a demented individual one needs to first assess safety concerns, then rule out delirium (including contributing medical disorders and medication effects), and pre-existing psychiatric illness. The agitation should then be described and the target behaviour identified. Appropriate treatment can be aimed at addressing the target behaviour.
• some behaviours that are relatively resistant to antipsychotic medication includes wandering, pacing, exit-seeking, and repetitive screaming and calling out
• nonpharmacological interventions can include following care schedules, avoiding stress, using simple verbal and non-verbal cueing, providing good personal care, good sleep hygiene, music therapy, appropriate lighting levels, appropriate environmental changes, and exit control
• it is important to nuture the personhood of the individual with dementia

Alzheimer Disease and Vascular Dementia

• 1/3-1/2 of autopsy proven Alzheimer's disease also has evidence of cerebrovascular disease
• a potential common risk factor is Apo E e4
• Apo E is involved in lipid transport and in the CNS is involved in mobilising lipids for growth and repair
• Apo Ee4 is associated with elevated plasma cholesterol, LDL, and atherosclerosis, and is also associated with late-onset Familial Alzheimer's disease and an increased risk of sporadic Alzheimer's disease
• Alzheimer's disease and cerebrovascular disease are both common and share risk factors
• Controlling hypertension in the Sys Euro trial (Lancet 1998) demonstrated a 50% reduction in the incidence of dementia
• There was a 60-73% reduction in dementia prevalence in individuals with hypercholesterolemia who were treated with a HMG-CoA reductase inhibitor (Arch Neurol 2000)
• there appears to be similar cholinergic deficits in Alzheimer's disease and Vascular dementia
• in preclinical models, rivastigmine has been shown to prevent a decrease in cholinergic indices in ischemic conditions and to prevent of post-ischemic neuronal death in the hippocampus
• The treatment effect of rivastigmine was higher in Alzheimer patients with vascular risk factors (ADAS cog Study 352)
• galantamine improved the ADAS cog scores by 2-3 points compared to placebo when given to individuals with probable Vascular dementia, intermediate Vascular dementia, or mixed Vascular dementia and Alzheimer's disease (Neurology 2001;s38:340)

Parkinson's disease and the Frail Elderly

• levodopa is still the gold standard for relief of Parkinson's disease symptoms
• the new dopamine agonists are devoid of the rare ergot-related toxicity but are equivalent in terms of other toxicity, including nausea, postural hypotension, and psychosis

For reviews of disturbing behaviour in dementia, Alzheimer Disease, Vascular Dementia and Parkinson's disease in the elderly, see our website at www.geriatricsandaging.ca.

A. Mark Clarfield, MD

In 1989 the first Canadian Consensus Conference on the Assessment of Dementia (CCCAD) met in Montreal to try to come to grips with the vexed question of dementia assessment. In those days, there was still a lively debate going about the extent to which dementia should be worked up in an attempt to find the "reversible" cases.

Nearly ten years later in 1998, the group reconvened to look at assessment again but extended its mandate as well. What follows is a brief "compare and contrast" essay which examines what the two meetings had in common as well as how they differed.

To start off, they were both held in the beautiful city of Montreal, in 1989 under the joint chairmanship of myself and Dr. Serge Gauthier. In 1998, Dr. Gauthier was still in charge but this time Dr. Chris Patterson of McMaster University joined as the co-chair. (In 1992, I had moved to Israel, but was honoured to be invited back.)

In 1989 before (or perhaps at the beginning of) the extensive government cutbacks, we were able to fund the meeting with 50% government money, both federal and Quebec provincial. The rest of the support came from private sources, mainly drug companies. By 1998 it seems that government wanted no part of consensus meetings at least in the field of the dementias, and they did not participate in the funding this time.

A decade ago the 38 participants were mainly Canadian with four American visitors.